Effect of a customized digital adherence tool on retention in care and adherence to antiretroviral treatment in breastfeeding women, children and adolescents living with HIV in Tanzania: a mixed-methods study followed by clinical trials.

BACKGROUND: Adherence to antiretroviral (ARV) treatment for HIV infection is challenging because of many factors. The World Health Organization (WHO) has recommended using digital adherence technologies (DATs). However, there is limited evidence on how DATs improve adherence. Wisepill® is an internet-enabled medication dispenser found feasible and acceptable in several studies. However, limited evidence is available on its effectiveness in improving ART adherence, specifically among children and adolescents. Furthermore, DATs are often developed without involving the target groups. We propose a two-stage project consisting of a formative study to customize an existing Wisepill DAT intervention and a randomized clinical trial to investigate the effectiveness of DAT combined with reminder cues and tailored feedback on adherence to ARV treatment among children and adolescents living with HIV and retention in care among breastfeeding women living with HIV in Kilimanjaro and Arusha Region, Tanzania. METHODS: We will conduct a formative mixed-methods study and three sub-trials in Kilimanjaro and Arusha Regions among (1) children aged 0-14 years and their caregivers, (2) adolescents aged 15-19 years and (3) breastfeeding women and their HIV-negative infants. In the formative study, we will collect and analyse data on needs and contents for DATs, including the contents of short message service (SMS) texts and tailored feedback. The results will inform the customization of the DAT to be tested in the sub-trials. In the trials, participants will be randomized in the intervention arm, where the DAT will be implemented or the control arm, where standard care will be followed. Participants in the intervention arm will take their medication from the Wisepill box and receive daily reminder texts and tailored feedback during clinic visits. DISCUSSION: If the intervention improves adherence to ART and the devices are acceptable, accurate and sustainable, the intervention can be scaled up within the National Aids Control Programmes. TRIAL REGISTRATION: PACTR202301844164954, date 27 January 2023.

Interruptions in treatment among adults on anti-retroviral therapy before and after test-and-treat policy in Tanzania.

INTRODUCTION: The World Health Organization recommended the initiation of antiretroviral therapy (ART) for people living with HIV (PLHIV) regardless of CD4 cell counts. Tanzania adopted this recommendation known as test-and-treat policy in 2016. However, programmatic implementation of this policy has not been assessed since its initiation. The objective of the study was to assess the impact of this policy in Tanzania. METHODS: This was a cross-sectional study among PLHIV aged 15 years and older using routinely collected program data. The dependent variable was interruption in treatment (IIT), defined as no clinical contact for at least 90 days after the last clinical appointment. The main independent variable was test-and-treat policy status which categorized PLHIV into the before and after groups. Co-variates were age, sex, facility type, clinical stage, CD4 count, ART duration, and body mass index. The associations were assessed using the generalized estimating equation with inverse probability weighting. RESULTS: The study involved 33,979 PLHIV-14,442 (42.5%) and 19,537 (57.5%) were in the before and after the policy groups, respectively. Among those who experienced IIT, 4,219 (29%) and 7,322 (38%) were in the before and after the policy groups respectively. Multivariable analysis showed PLHIV after the policy was instated had twice [AOR 2.03; 95%CI 1.74-2.38] the odds of experiencing IIT than those before the policy was adopted. Additionally, higher odds of experiencing IIT were observed among younger adults, males, and those with advanced HIV disease. CONCLUSION: Demographic and clinical status variables were associated with IIT, as well as the test-and-treat policy. To achieve epidemic control, programmatic adjustments on continuity of treatment may are needed to complement the programmatic implementation of the policy.

Prevalence of substance use and associated factors among secondary school adolescents in Kilimanjaro region, northern Tanzania.

BACKGROUND: Substance use among school-going adolescents increases the risk of developing mental disorders, addiction, and substance use disorders. These may lead to poor academic performance and reduced productivity, which affects adolescent lives. The study aimed to determine the prevalence of substance use and associated factors among secondary school adolescents in the Kilimanjaro region, northern Tanzania. METHODOLOGY: The study used secondary data from a cross-sectional survey of adolescents aged 10-19 years from public secondary schools in the Kilimanjaro Region, northern Tanzania. Substance use was measured using the Global School Health Survey (GSHS) questionnaire. Categorical variables were summarized using frequencies and percentages, while numerical variables used mean and standard deviation. Multivariable logistic regression models were used to obtain odds ratios (OR) and 95% confidence intervals (CI) to determine risk factors associated with lifetime and current (within the past 30 days preceding the survey) substance use. RESULTS: The lifetime and current prevalence of substance use among 3224 adolescents was 19.7% and 12.8%, respectively, while alcohol and cigarettes were commonly used. Female adolescents had lower odds of current substance use (OR = 0.63, 95%CI 0.50-0.80). Higher odds of current substance use were among adolescents who have ever had sex (OR = 4.31, 95%CI 3.25-5.71), ever engaged in a physical fight (OR = 2.19, 95%CI 1.73-2.78), ever been bullied (OR = 1.55, 95%CI 1.16-2.05), always seen alcohol advertisements (OR = 1.87, 95%CI 1.37-2.53), and adolescents whose parent/guardians rarely understood their problems (OR = 1.38, 95% CI = 1.03-1.85). Adolescents whose classmates always showed social support had lower odds of current substance use (AOR = 0.71, 95%CI 0.53-0.97). Similar factors were associated with lifetime substance users. CONCLUSION: The study reflects a high prevalence of substance use among adolescents in the Kilimanjaro region. Alcohol and cigarette are the most prevalent substances used. Regulatory measures are essential to limit alcohol advertisements that are media portrayed. Efforts are needed to reduce risk behaviors, such as physical violence and bullying, through peer support groups/clubs in school environments.

Complete glutathione system in probiotic Lactobacillus fermentum ME-3.

There is much information about glutathione (GSH) in eukaryotic cells, but relatively little is known about GSH in prokaryotes. Without GSH and glutathione redox cycle lactic acid bacteria (LAB) cannot protect themselves against reactive oxygen species. Previously we have shown the presence of GSH in Lactobacillus fermentum ME-3 (DSM14241). Results of this study show that probiotic L. fermentum ME-3 contains both glutathione peroxidase and glutathione reductase. We also present that L. fermentum ME-3 can transport GSH from environment and synthesize GSH. This means that it is characterized by a complete glutathione system: synthesis, uptake and redox turnover ability that makes L. fermentum ME-3 a perfect protector against oxidative stress. To our best knowledge studies on existence of the complete glutathione system in probiotic LAB strains are still absent and glutathione synthesis in them has not been demonstrated.

Functional Impairment of Skin Appendages Due to Peripheral Nerve Involvement by Mycobacterium leprae.

In the earliest stage of Mycobacterium leprae infection, bacteria parasitize fine fiber twigs of autonomic peripheral nerves supplying efferent impulses to appendages of the skin. This obligate intracellular pathogen invades Schwann cells, the glial cells of peripheral nerves. Intracellular events inhibit Schwann cell physiology in complex ways, which include demyelination and dedifferentiation. Ultimately, axons embraced by their surrounding dysfunctional glia are damaged by poorly understood mechanisms. Loss of nerve conduction impairs the functions of skin appendages including hair growth, sebaceous gland secretion, sweating, and skin pigmentation. At the clinical level, these changes may be subtle and may precede the more obvious anesthetic skin lesions associated with Hansen's disease. Recognizing the early signs of skin appendage malfunction may aid in diagnosis leading to initiation of antimycobacterial treatment. Effective therapy administered early during infection may prevent irreversible peripheral nerve destruction, the presage for morbid complications of leprosy.

Oxidative stress in leucocytospermic prostatitis patients: preliminary results.

The aim of this study was to contribute to the knowledge concerning pathogenesis of inflammatory chronic prostatitis by revealing possible shifts in the balance of markers of oxidative stress and anti-oxidative activity in case of leucocytospermic prostatitis. We also attempted to identify possible relations between seminal micro-organisms and oxidative stress parameters. A many-sided complex of local (spermatozoa, seminal plasma) and general (blood, urine) markers in 21 prostatitis patients and nine controls was compared. In both spermatozoa and seminal plasma, the content of diene conjugates was significantly higher in prostatitis patients compared with healthy controls. At the same time total anti-oxidative status in spermatozoa and total anti-oxidative activity in seminal plasma were lower in prostatitis patients than in controls. In urine, the level of 8-isoprostanes was significantly higher in prostatitis patients than in healthy controls, correlating well with 8-hydroxy-2'-deoxyguanosine. The latter correlated with cellular Fe and Ni contents as well, confirming that these metals with varying valency may cause DNA damage. Reduced glutathione showed higher levels in blood of controls than in prostatitis patients. Coryneform bacteria appeared to be associated with prostatitis-related oxidative stress. In conclusion, leucocytospermic prostatitis patients are characterised by oxidative stress at all levels: systemic (general), seminal plasma and cellular.

Patients with allergic and irritant contact dermatitis are characterized by striking change of iron and oxidized glutathione status in nonlesional area of the skin.

To assess the consequences of oxidative stress in allergic and irritant contact dermatitis, we compared the iron level, unsaturated iron-binding capacity, total iron binding capacity, the percentage saturation of iron-binding capacity, the amount of diene conjugates as well as the amounts of total glutathione, reduced glutathione, oxidized glutathione, and the oxidized glutathione/reduced glutathione ratio in skin homogenate from lesional and nonlesional skin. Lesional skin samples were obtained from positive patch test sites to 5% NiSO4 in five subjects, and from chronic contact dermatitis lesions on the hands, which had exacerbated over 3--9 wk in six subjects. Contact dermatitis caused at least a 4-fold increase in the iron level in the lesional skin area compared with the nonlesional skin area (p < 0.02). The increase in the iron level depended on the duration of contact dermatitis and was accompanied by high unsaturated iron-binding capacity and total iron-binding capacity values in the positive patch test sites (p < 0.05), and by a high percentage saturation value in the chronic contact dermatitis lesions (p < 0.05). We found high indices for iron, total iron-binding capacity and diene conjugates in the apparently healthy skin of the patients with persistent contact dermatitis that significantly (p < 0.05) exceeded the corresponding values in the patients with only patch test reactions. In summary, we have succeeded in providing evidence that generalized oxidative damage of the skin occurs as a consequence of contact dermatitis in a restricted area.

Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania.

Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.

The Swedish APP670/671 Alzheimer's disease mutation: the first evidence for strikingly increased oxidative injury in the temporal inferior cortex.

To evaluate the level of oxidative stress (OS) in familial Alzheimer's disease (FAD), we analysed four cerebrocortical areas from patients with Swedish FAD bearing the APP670/671 mutation. The temporal inferior cortex (TIC) from Swedish FAD patients revealed a striking 2- to 3-fold increase in diene conjugates, lipid peroxides and protein carbonyls, compared to sporadic Alzheimer's disease (AD). Compared with TIC from sporadic AD patients, the mutation carriers showed a markedly decreased activity of catalase (CAT) in the same area, and the same trend was found for another antioxidant enzyme, superoxide dismutase. These results are consistent with the deep oxidative injury of TIC in Swedish FAD. In the frontal inferior cortex (FIC), sensory postcentral cortex (SPCC) and occipital primary cortex (OPC) from Swedish FAD, the parameters of oxidative injury tended to be higher than in sporadic AD. Only the increase in the levels of lipid hydroperoxides in SPCC and of protein carbonyls in OPC was significant. Compared to sporadic AD, Swedish FAD showed a significant increase in GSSG levels and the GSSG/2GSH ratio in the FIC, SPCC and OPC. A significantly decreased activity of CAT was detectable for the SPCC and OPC in Swedish FAD. Increased OS might play a crucial role in the rapid progression of Swedish FAD from the associative temporal cortex to the primary cerebrocortical areas.

Could long-term alimentary iron overload have an impact on the parameters of oxidative stress? A study on the basis of a village in southern Estonia.

The effects of long-term alimentary (drinking water) iron overload on the parameters of oxidative stress were evaluated. The study group (n = 35) from a village in southern Estonia was 37.1 +/- 13.3 years old, and the mean period of drinking water iron overload was 20.6 +/- 9.3 years. The serum iron content was significantly higher than normal. The total iron-binding capacity of serum tended to be lowered. There was no change in the transferrin content. The parameters of lipid peroxidation like conjugated dienes and thiobarbituric acid reactive substances showed also significant differences. In addition, the red blood cell glutathione content was also decreased. The total antioxidant capacity of serum was not changed. It can be concluded from our results that a long-term alimentary iron overload results in a positive serum iron balance, which, in turn, yields an increased oxidative stress.